Comprehensive exome profiling identifies mutation as a driver in gastric cancer with ovarian metastasis.

Gastric cancer (GC) with ovarian metastasis (OM) represents a distinct subtype of peritoneal metastasis in female patients, characterized by limited therapeutic options and poor prognosis, with molecular features and mechanisms that remain unknown. We performed whole-exome sequencing (WES) analysis of matched GC samples, with OM or peritoneal metastasis (PM), to identify mutational profiles that contribute to OM. We further validate these findings through in vitro and in vivo experiments.

Automated interpretation of PD-L1 CPS based on multi-AI models integration strategy in gastric cancer.

Introduction: Programmed cell death ligand-1 (PD-L1) combined positive score (CPS) evaluation plays a pivotal role in predicting immunotherapy efficacy for gastric cancer. However, manual CPS assessment suffers from significant inter-observer variability among pathologists, leading to clinical inconsistencies. To address this limitation, we developed a deep learning-based artificial intelligence (AI) system that automates PD-L1 CPS quantification for patients with gastric cancer (GC) using whole slide images (WSIs).

The RNA mA landscape during human oocyte-to-embryo transition.

RNA N-methyladenosine (mA, m6A) modification is a critical regulator for a range of physiological processes. However, the dynamic mA profiles within human preimplantation embryos remain uncharacterized. Here, we present the first RNA mA landscape of single human oocytes and early embryos.

CRISPR/Cas-mediated mRNA knockdown in the embryos of Xenopus tropicalis.

The Xenopus tropicalis (Western clawed frog) is an important amphibian model for genetics, developmental and regenerative biology, due to its diploid genetic background and short generation time. CRISPR-Cas13 and CRISPR interference (CRISPRi) systems have recently been employed to suppress mRNA expression in many organisms such as yeast, plants, and mammalian cells. However, no systematic study of these two systems has been carried out in Xenopus tropicalis.

Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype.

Immunotherapy has revolutionized cancer treatment, but response variability remains a challenge. The gut microbiome's role in therapeutic efficacy is well established, but the impact of the gut mycobiome is less understood. Using unsupervised clustering, we identify two gut mycobiome-based enterotypes, favorable type and unfavorable type, characterized by distinct microbial compositions linked to immunotherapy outcomes.

Screening of patient-derived organoids identifies mitophagy as a cell-intrinsic vulnerability in colorectal cancer during statin treatment.

Statins, commonly used to lower cholesterol, are associated with improved prognosis in colorectal cancer (CRC), though their effectiveness varies. This study investigates the anti-cancer effects of atorvastatin in CRC using patient-derived organoids (PDOs) and PDO-derived xenograft (PDOX) models. Our findings reveal that atorvastatin induces mitochondrial dysfunction, leading to apoptosis in cancer cells.

FoxO3 controls cardiomyocyte proliferation and heart regeneration by regulating Sfrp2 expression in postnatal mice.

The Forkhead box O3 (FoxO3) transcription factor is crucial to controlling heart growth in adulthood, but its exact role in cardiac repair and regeneration in postnatal mice remains unclear. Here, we show that FoxO3 deficiency promotes cardiomyocyte proliferation in postnatal mice and improves cardiac function in homeostatic adult mice. Moreover, FoxO3 deficiency accelerates heart regeneration following injury in postnatal mice at the regenerative and non-regenerative stages.

Interplay between gut microbial communities and metabolites modulates pan-cancer immunotherapy responses.

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but remains effective in only a subset of patients. Emerging evidence suggests that the gut microbiome and its metabolites critically influence ICB efficacy. In this study, we performed a multi-omics analysis of fecal microbiomes and metabolomes from 165 patients undergoing anti-programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy, identifying microbial and metabolic entities associated with treatment response.

Cardiomyocyte proliferation and heart regeneration in adult Xenopus tropicalis evidenced by a transgenic reporter line.

Cardiomyocyte proliferation in adult Xenopus tropicalis during heart regeneration has remained largely contentious due to the absence of genetic evidence. Here, we generated a transgenic reporter line Tg(mlc2:H2C) expressing mCherry specifically in cardiomyocyte nuclei driven by the promoter of myosin light chain 2 (mlc2). Using the reporter line, we found that traditional whole-cell staining is not a rigorous way to identify cardiomyocytes in adult Xenopus tropicalis when using a cryosection with common thickness (5 μm) which leading to a high error, but this deviation could be reduced by increasing section thickness.

Gastrodin ameliorates diabetic nephropathy by activating the AMPK/Nrf2 pathway.

Diabetic nephropathy (DN) is a leading cause of end-stage kidney failure, contributing to elevated morbidity and mortality rates in individuals with diabetes. Despite its potential renoprotective effects, the molecular mechanism by which gastrodin (GSTD) impacts DN remains unclear. To investigate this, mice were initially induced with DN via intraperitoneal streptozotocin (STZ) injection (50 mg/kg) and subsequently treated with varying doses of GSTD (5, 10, 20 mg/kg).

Single-cell RNA transcriptomic analyses of tumor microenvironment of ovarian metastasis in gastric cancer.

Purpose: Ovarian metastasis of gastric cancer (GC), commonly referred to as Krukenberg tumors, leads to a poor prognosis. However, the cause of metastasis remains unknown. Here, we present an integrated single-cell RNA sequencing (scRNA-Seq) analysis of the immunological microenvironment of two paired clinical specimens with ovarian metastasis of GC.

Building consensus on the application of organoid-based drug sensitivity testing in cancer precision medicine and drug development.

Patient-derived organoids (PDOs) have emerged as a promising platform for clinical and translational studies. A strong correlation exists between clinical outcomes and the use of PDOs to predict the efficacy of chemotherapy and/or radiotherapy. To standardize interpretation and enhance scientific communication in the field of cancer precision medicine, we revisit the concept of PDO-based drug sensitivity testing (DST).

Hepatocyte-specific METTL3 ablation by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), resulted in acute liver failure (ALF) and postnatal lethality.

Aim: In 2019, to examine the functions of METTL3 in liver and underlying mechanisms, we generated mice with hepatocyte-specific METTL3 homozygous knockout (METTL3Δhep) by simultaneously crossing METTL3fl/fl mice with Alb-iCre mice (GPT) or Alb-Cre mice (JAX), respectively. In this study, we explored the potential reasons why hepatocyte-specific METTL3 homozygous disruption by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), resulted in acute liver failure (ALF) and then postnatal lethality.

Main Methods: Mice with hepatocyte-specific METTL3 knockout were generated by simultaneously crossing METTL3fl/fl mice with Alb-iCre mice (GPT; Strain No.

Predictive value of positive lymph node ratio in patients with locally advanced gastric remnant cancer.

Background: Traditional lymph node stage (N stage) has limitations in advanced gastric remnant cancer (GRC) patients; therefore, establishing a new predictive stage is necessary.

Aim: To explore the predictive value of positive lymph node ratio (LNR) according to clinicopathological characteristics and prognosis of locally advanced GRC.

Methods: Seventy-four patients who underwent radical gastrectomy and lymphadenectomy for locally advanced GRC were retrospectively reviewed.

Gut microbiome for predicting immune checkpoint blockade-associated adverse events.

Background: The impact of the gut microbiome on the initiation and intensity of immune-related adverse events (irAEs) prompted by immune checkpoint inhibitors (ICIs) is widely acknowledged. Nevertheless, there is inconsistency in the gut microbial associations with irAEs reported across various studies.

Methods: We performed a comprehensive analysis leveraging a dataset that included published microbiome data (n = 317) and in-house generated data from 16S rRNA and shotgun metagenome samples of irAEs (n = 115).

Faecalibacterium prausnitzii Abrogates Intestinal Toxicity and Promotes Tumor Immunity to Increase the Efficacy of Dual CTLA4 and PD-1 Checkpoint Blockade.

Unlabelled: Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy; however, their application is limited by the occurrence of immune-related adverse events. The gut microbiota plays important roles in the response to and toxicity of immunotherapy and Faecalibacterium prausnitzii (F. prausnitzii) has been shown to possess immunomodulatory potential.

Hairy gene homolog increases nasopharyngeal carcinoma cell stemness by upregulating .

B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) is overexpressed in various cancer types. We found that mRNA levels were elevated in nasopharyngeal carcinoma (NPC) cell lines. In immunohistochemical analyses, high Bmi-1 levels were observed in not only 5 of 38 non-cancerous nasopharyngeal squamous epithelial biopsies, but also in 66 of 98 NPC specimens (67.

Fusobacterium nucleatum-derived succinic acid induces tumor resistance to immunotherapy in colorectal cancer.

Immune checkpoint blockade therapy with anti-PD-1 monoclonal antibody (mAb) is a treatment for colorectal cancer (CRC). However, some patients remain unresponsive to PD-1 blockade. The gut microbiota has been linked to immunotherapy resistance through unclear mechanisms.

MicroRNA-155 suppressed cholesterol-induced matrix degradation, pyroptosis and apoptosis by targeting RORα in nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is associated with low back pain, yet its inherent mechanism remains obscure. Hypercholesteremia was regarded as a risk factor for IDD, and our previous study showed that cholesterol accumulation could elicit matrix degradation in the nucleus pulposus (NP). MicroRNA-155 (miR-155) was substantiated as protective in IDD, but its role in cholesterol-induced IDD was unclear.

regulates osteogenesis and bone mass phenotype via targeting gene.

MicroRNA-155 (miR155) is overexpressed in various inflammatory diseases and cancer, in which bone resorption and osteolysis are frequently observed. However, the role of miR155 on osteogenesis and bone mass phenotype is still unknown. Here, we report a low bone mass phenotype in the long bone of -Tg mice compared with wild-type mice.

Regulation mechanism of ferroptosis and its research progress in tumor immunotherapy.

Ferroptosis is a novel regulatory cell death, which is characterized by iron dependency and mainly caused by accumulation of intracellular lipid peroxides and reactive oxygen species. Ferroptosis plays an important role in the occurrence and development of a variety of malignant tumors, especially in anti-tumor treatment. As an emerging treatment method, the immunotherapy has been widely applied in the clinical practice, and the role of ferroptosis in tumor immunotherapy has been gradually explored.